Single-nuclei sequencing of the mouse hippocampus of dietary restricted mice

Dietary restriction (DR), reduced food intake while avoiding malnutrition, profoundly extends lifespan in most model and non-model organisms. Both chronic (i.e. life-long) and acute (i.e. late-onset) DR have been shown to improve cognitive performance in aged mice compared to animals with an unrestricted access to food (ad libitium feeding; AL). Yet so far, quantitative analyses of the molecular dynamics in the brain of DR fed animals have been limited. Here we performed single-nuclei sequencing (Nuc-seq) of whole hippocampus isolated from young (5 months) and old (24 months) AL fed animals, as well as old chronic DR (DR started at 3 months) and acute DR (aDR) mice. Single-nuclei RNA transcriptomes of whole frozen hippocampus obtained from brains of young (5 months) and old (24 months) mice fed ad libitum (AL) as well as old mice that were dietary restricted from the age of 5 months (long-term DR; DR) or 20 months of age (acute DR; aDR) using 10x Genomics Drop-seq (v3.0). All animals were of the C3B6F1 hybrid strain.饮食限制（Dietary Restriction, DR）指在避免营养不良的前提下减少食物摄入，该干预手段可在绝大多数模式生物与非模式生物中显著延长寿命。相较于自由采食（ad libitum feeding, AL）的对照组动物，长期（即终生）与急性（即晚期启动）饮食限制均被证实可改善老年小鼠的认知功能。然而迄今为止，针对饮食限制动物脑部分子动态变化的定量分析仍较为有限。本研究针对年轻（5月龄）、老年（24月龄）自由采食小鼠，以及3月龄起启动长期饮食限制的老年小鼠、急性饮食限制（acute DR, aDR）小鼠的全海马组织开展了单细胞核测序（single-nuclei sequencing, Nuc-seq）；随后采用10x Genomics Drop-seq（v3.0）技术，对上述自由采食小鼠，以及5月龄起启动长期饮食限制（long-term DR, DR）、20月龄起启动急性饮食限制（acute DR, aDR）的老年小鼠的冷冻全海马组织完成了单细胞核RNA转录组测序。所有实验动物均为C3B6F1杂交品系。